tbuckley/cabot-search huggingface dataset:
Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE.
Authors: Sebastian Bauer, Robin Lewis Jones, Suzanne George, Hans Gelderblom, Patrick Schöffski, Margaret von Mehren, John Raymond Zalcberg, Yoon-Koo Kang, Albiruni Ryan Abdul Razak, Jonathan C. Trent, Steven Attia, Axel Le Cesne, William Reichmann, Kam Sprott, Haroun Achour, Matthew L. Sherman, Rodrigo Ruiz-Soto, Jean-Yves Blay, Michael C. Heinrich
Journal: Journal of Clinical Oncology (2023)

397784 Background: Ripretinib, a switch-control tyrosine kinase inhibitor (TKI), is indicated for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with ≥3 TKIs, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. Circulating tumor DNA (ctDNA) analysis may provide insight into the efficacy of these agents in second-line advanced GIST. Here, we present exploratory baseline ctDNA results from INTRIGUE. Methods: INTRIGUE is an open-label, phase 3 study that enrolled adult pts with advanced GIST who progressed on or had intolerance to imatinib (NCT03673501). Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off). Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing (NGS)-based assay. Only KIT mutations are reported here. Results: Of 453 pts in the overall intent-to-treat (ITT) population, 362 (80%) samples were analyzed. ctDNA was detected in 280/362 (77%), with KIT mutations detected in 213/280 (76%). Common resistance mutations were in the KIT activation loop (AL; exons 17/18; 89/213, 42%) and ATP-binding pocket (ATP-BP; exons 13/14; 81/213, 38%). Efficacy in pts with detectable ctDNA in the KIT exon 11 and overall ITT populations was consistent with the primary analysis based on tumor data used for randomization. Pts with KIT exon 11 + 17/18 (−9/13/14) mutations had superior progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) with ripretinib vs sunitinib, whereas pts with exon 11 + 13/14 (−9/17/18) mutations had better PFS, ORR, and OS with sunitinib vs ripretinib (Table). Subgroup safety profiles were consistent with the primary analysis. Conclusions: While KIT ATP-BP mutations predicted clinical benefit from sunitinib vs ripretinib, pts harboring resistance mutations in the KIT AL derived meaningful clinical benefit from ripretinib but not sunitinib. This study demonstrates the value of ctDNA NGS-based sequencing of the complex landscape of KIT mutations to predict the clinical benefit of ripretinib or sunitinib as second-line therapy in pts with advanced GIST. Clinical trial information: NCT03673501 . [Table: see text]
Endoscopic Duodenal-Jejunal Bypass Liner Treatment for Type 2 Diabetes and Obesity: Glycemic and Cardiovascular Disease Risk Factor Improvements in 1,022 Patients Treated Worldwide
Authors: Robert E.J. Ryder, Katharina Laubner, Marek Benes, Martin Haluzik, Lynne Munro, Harry Frydenberg, Julian P. Teare, Aruchuna Ruban, Sigal Fishman, Erwin Santo, Rainer Stengel, Charlotte De Jonge, Jan W. Greve, Ricardo V. Cohen, Cristina M. Aboud, Gerald J. Holtmann, Graeme Rich, Jess J. McMaster, Tadej Battelino, Primoz Kotnik, James P. Byrne, John C. Mason, Justin Bessell, Jeanine Bascomb, Lillian Kow, Janes Collins, Jacob Chisholm, Peter N. Pferschy, Harald Sourij, Melissa L. Cull, Melanie C. Wyres, Russell Drummond, Barbara McGowan, Stephanie A. Amiel, Mahi Yadagiri, Piya Sen Gupta, Jens Aberle, Jochen Seufert
Journal: Diabetes Care (2023)
<i>Roe v Wade</i>’s 50th Anniversary
Authors: Rebecca B. Reingold, Lawrence O. Gostin
Journal: JAMA (2023)

This Viewpoint summarizes several federal strategies to ensure pregnant persons’ access to abortion services after the recent Supreme Court ruling in Dobbs v Jackson Women’s Health Organization: expanding access to medication abortion, ensuring provision of emergency abortion services, proposing new conscience protections for clinicians, and protecting reproductive rights at the state level.
Autism, Physical Health Conditions, and a Need for Reform
Authors: Elizabeth M. Weir
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Changes in Prescribed Opioid Dosages Among Patients Receiving Medical Cannabis for Chronic Pain, New York State, 2017-2019
Authors: Trang Nguyen, Yunshu Li, Danielle Greene, Sharon Stancliff, Nicole Quackenbush
Journal: JAMA Network Open (2023)

Patients with chronic pain often receive long-term opioid therapy (LOT), which places them at risk of opioid use disorder and overdose. This presents the need for alternative or companion treatments; however, few studies on the association of medical cannabis (MC) with reducing opioid dosages exist.To assess changes in opioid dosages among patients receiving MC for longer duration compared with shorter duration.This cohort study of New York State Prescription Monitoring Program data from 2017 to 2019 included patients receiving MC for chronic pain while also receiving opioid treatment. Of these, patients receiving LOT prior to receiving MC were selected. Individuals were studied for 8 months after starting MC. Data were analyzed from November 2021 to February 2022.Selected patients were divided into 2 groups based on the duration of receiving MC: the nonexposure group received MC for 30 days or fewer, and the exposure group received MC for more than 30 days.The main outcome was opioid dosage, measured by mean daily morphine milligram equivalent (MME). Analyses were conducted for 3 strata by opioid dosage prior to receiving MC: MME less than 50, MME of 50 to less than 90, and MME of 90 or greater.A total of 8165 patients were included, with 4041 (median [IQR] age, 57 [47-65] years; 2376 [58.8%] female) in the exposure group and 4124 (median [IQR] age, 54 (44-62) years; 2370 [57.5%] female) in the nonexposure group. Median (IQR) baseline MMEs for the exposure vs nonexposure groups were 30.0 (20.0-40.0) vs 30.0 (20.0-40.0) in the lowest stratum, 60.0 (60.0-70.0) vs 60.0 (60.0-90.0) in the middle stratum, and 150.0 (100.0-216.2) vs 135.0 (100.0-218.0) in the highest stratum. During follow-up, significantly greater reductions in opioid dosage were observed among the exposure group. A dose-response association of patients' opioid dosage at baseline was observed with the differences in the monthly MME reductions between exposure and nonexposure groups, with a difference of -1.52 (95% CI, -1.67 to -1.37) MME for the lowest stratum, -3.24 (95% CI, -3.61 to -2.87) MME for the middle stratum, and -9.33 (95% CI, -9.89 to -8.77) MME for the highest stratum. The daily MME for the last month of the follow-up period among patients receiving longer MC was reduced by 48% in the lowest stratum, 47% in the middle stratum, and 51% in the highest stratum compared with the baseline dosages. Among individuals in the nonexposure group, daily MME was reduced by only 4% in the lowest stratum, 9% in the middle stratum, and 14% in the highest stratum.In this cohort study of patients receiving LOT, receiving MC for a longer duration was associated with reductions in opioid dosages, which may lower their risk of opioid-related morbidity and mortality.
Association of Maternal Depression During Pregnancy and Recent Stress With Brain Age Among Adult Offspring
Authors: Klara Mareckova, Radek Mareček, Martin Jani, Lenka Zackova, Lenka Andryskova, Milan Brazdil, Yuliya S. Nikolova
Journal: JAMA Network Open (2023)

Importance Maternal mental health problems during pregnancy are associated with altered neurodevelopment in offspring, but the long-term relationship between these prenatal risk factors and offspring brain structure in adulthood remains incompletely understood due to a paucity of longitudinal studies. Objective To evaluate the association between exposure to maternal depression in utero and offspring brain age in the third decade of life, and to evaluate recent stressful life events as potential moderators of this association. Design, Setting, and Participants This cohort study examined the 30-year follow-up of a Czech prenatal birth cohort with a within-participant design neuroimaging component in young adulthood conducted from 1991 to 2022. Participants from the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort were recruited for 2 magnetic resonance imaging (MRI) follow-ups, one between ages 23 and 24 years (early 20s) and another between ages 28 and 30 years (late 20s). Exposures Maternal depression during pregnancy; stressful life events in the past year experienced by the young adult offspring. Main Outcomes and Measures Gap between estimated neuroanatomical vs chronological age at MRI scan (brain age gap estimation [BrainAGE]) calculated once in participants’ early 20s and once in their late 20s, and pace of aging calculated as the differences between BrainAGE at the 2 MRI sessions in young adulthood. Results A total of 260 individuals participated in the second neuroimaging follow-up (mean [SD] age, 29.5 [0.6] years; 135 [52%] male); MRI data for both time points and a history of maternal depression were available for 110 participants (mean [SD] age, 29.3 [0.6] years; 56 [51%] male). BrainAGE in participants’ early 20s was correlated with BrainAGE in their late 20s ( r = 0.7, P &amp;amp;lt; .001), and a previously observed association between maternal depression during pregnancy and BrainAGE in their early 20s persisted in their late 20s (adjusted R 2 = 0.04; P = .04). However, no association emerged between maternal depression during pregnancy and the pace of aging between the 2 MRI sessions. The stability of the associations between maternal depression during pregnancy and BrainAGE was also supported by the lack of interactions with recent stress. In contrast, more recent stress was associated with greater pace of aging between the 2 MRI sessions, independent of maternal depression (adjusted R 2 = 0.09; P = .01). Conclusions and Relevance The findings of this cohort study suggest that maternal depression and recent stress may have independent associations with brain age and the pace of aging, respectively, in young adulthood. Prevention and treatment of depression in pregnant mothers may have long-term implications for offspring brain development.
Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults With Obesity
Authors: Ying Chen, Zheng Chen, Lingling Pan, Zhi-Min Ma, Huijie Zhang, Xue-Jun Li, Xiaoying Li
Journal: JAMA Internal Medicine (2023)

This randomized clinical trial assesses the long-term effect of vigorous and moderate exercise on incident diabetes over a 10-year follow-up after a 12-month exercise intervention.
Are We Ready for Prehospital Troponin Testing?
Authors: Isabel R. Ostrer, Tracy Y. Wang
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Wide QRS Complex Tachycardia Change to Narrow QRS Complex Tachycardia After β-Blocker Administration
Authors: Jun-Peng Liu, Wen-Duo Zhang, Hua Wang
Journal: JAMA Internal Medicine (2023)

This case report describes a patient in their 80s with a history of paroxysmal atrial fibrillation who presented with palpitation, dizziness, nausea, and vomiting.
Assessment of Quality of Life Among Patients With Recurrent Clostridioides difficile Infection Treated with Investigational Oral Microbiome Therapeutic SER-109
Authors: Kevin W. Garey, Jinhee Jo, Anne J. Gonzales-Luna, Brittany Lapin, Abhishek Deshpande, Elaine Wang, Brooke Hasson, Sissi V. Pham, Shirley P. Huang, Pat Ray Reese, Henry Wu, Elizabeth Hohmann, Paul Feuerstadt, Caterina Oneto, Charles S. Berenson, Christine Lee, Barbara McGovern, Lisa vonMoltke
Journal: JAMA Network Open (2023)

Importance Recurrent Clostridioides difficile infection (CDI) is a debilitating disease leading to poor health-related quality of life (HRQOL), loss of productivity, anxiety, and depression. The potential association of treatment with HRQOL has not been well evaluated. Objectives To explore the association of SER-109 compared with placebo on HRQOL in patients with recurrent CDI up to week 8. Design, Setting, and Participants This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial that took place at 56 sites in the US and Canada from July 2017 to April 2020 and included 182 patients randomized to SER-109 or placebo groups. Interventions SER-109 or placebo (4 capsules once daily for 3 days) following antibiotics for CDI. Main Outcomes and Measures Exploratory analysis of HRQOL using the disease specific Clostridioides difficile Quality of Life Survey (Cdiff32) assessed at baseline, week 1, and week 8. Results In this study, 182 patients (109 [59.9%] female; mean age, 65.5 [16.5] years) were randomized to SER-109 (89 [48.9%]) or placebo (93 [51.1%]) groups and were included in the primary and exploratory analyses. Baseline Cdiff32 scores were similar between patients in the SER-109 and placebo groups (52.0 [18.3] vs 52.8 [18.7], respectively). The proportion of patients with overall improvement from baseline in the Cdiff32 total score was higher in the SER-109 arm than placebo at week 1 (49.4% vs 26.9%; P = .012) and week 8 (66.3% vs 48.4%; P = .001).Greater improvements in total and physical domain and subdomain scores were observed in patients in the SER-109 group compared with placebo as early as week 1, with continued improvements observed at week 8. Among patients in the placebo group, improvements in HRQOL were primarily observed in patients with nonrecurrent CDI while patients in the SER-109 group reported improvements in HRQOL, regardless of clinical outcome. Conclusions and Relevance In this secondary analysis of a phase 3 clinical trial, SER-109, an investigational microbiome therapeutic was associated with rapid and steady improvement in HRQOL compared with placebo through 8 weeks, an important patient-reported outcome. Trial Registration ClinicalTrials.gov Identifier: NCT03183128
Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy
Authors: Nagita Devi, Priyanka Madaan, Nidhun Kandoth, Dipika Bansal, Jitendra Kumar Sahu
Journal: JAMA Pediatrics (2023)

Importance Despite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions. Objective To evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy. Data Sources Systematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet , medium chain triglyceride diet , modified Atkins diet , low glycemic index therapy , and refractory epilepsy . Study Selection Randomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers. Data Extraction and Synthesis Data extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve. Main Outcomes and Measures Short-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes. Results Of 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event–related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes. Conclusions and Relevance This study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.
Initiation of and Escalation to High-Intensity Drinking in Young Adults
Authors: Megan E. Patrick, Rebecca J. Evans-Polce, Brooke J. Arterberry, Yvonne Terry-McElrath
Journal: JAMA Pediatrics (2023)

Importance High-intensity drinking (HID) (≥10 drinks in a row) is associated with acute negative outcomes. Identifying factors associated with HID initiation in adolescence and how it is associated with young adulthood outcomes can inform screening and prevention. Objective To identify when individuals initiate HID and speed of escalation from first drink and first binge to first HID; characteristics associated with initiation and escalation; and whether these characteristics are associated with weekly alcohol consumption, HID frequency, and symptoms of alcohol use disorder at age 20 years. Design, Setting, and Participants This cohort study analyzed web-based survey data from respondents in the US who reported alcohol use in the past 30 days recruited from the 2018 12th grade Monitoring the Future study and surveyed again from February 14 through April 17, 2020, at modal age 20 years in the Young Adult Daily Life Study. Only respondents who reported HID by modal age 20 years were included in the analyses. Exposures Retrospective alcohol use initiation and self-reported alcohol use measures. Main Outcomes and Measures Key retrospective measures included year of initiation for alcohol, first binge (≥5 drinks), and HID (≥10 drinks). Measures at age 20 years included weekly alcohol consumption, HID frequency, and Alcohol Use Disorders Identification Test (AUDIT) scores. Covariates included biologic sex, race and ethnicity, parental college education, family history of alcohol problems, and college status. Descriptive statistics and multivariable regression models were used, and all analyses were weighted. Results Of the 451 participants with data eligible for analysis, 62.0% were male (38.0% female). On average, alcohol, binge, and HID were initiated during high school. Mean time of escalation from first drink to first HID was 1.9 (95% CI, 1.8-2.1) years and between first binge and first HID, 0.7 (95% CI, 0.6-0.8) years. Initiating HID by grade 11 (vs later) was associated with higher average weekly alcohol consumption (adjusted incidence rate ratio [aIRR], 1.40; 95% CI, 1.10-1.79]), HID frequency (aIRR, 2.01; 95% CI, 1.25-3.22]), and AUDIT score (adjusted odds ratio, 1.17; 95% CI, 1.02-1.34]) at age 20 years. Escalation from first binge to first HID in the same year (vs ≥1 year) was associated with higher HID frequency at age 20 years (aIRR, 1.66; 95% CI, 1.06-2.61). Conclusions and Relevance These findings suggest that understanding ages and patterns of HID initiation and escalation associated with particular risk may facilitate screening for adolescents and young adults.
Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL
Authors: Andreas Hochhaus, Delphine Réa, Carla Boquimpani, Yosuke Minami, Jorge E. Cortes, Timothy P. Hughes, Jane F. Apperley, Elza Lomaia, Sergey Voloshin, Anna Turkina, Dong-Wook Kim, Andre Abdo, Laura Maria Fogliatto, Philipp le Coutre, Koji Sasaki, Dennis Dong Hwan Kim, Susanne Saussele, Mario Annunziata, Naeem Chaudhri, Lynette Chee, Valentin García-Gutiérrez, Shruti Kapoor, Alex Allepuz, Sara Quenet, Véronique Bédoucha, Michael J. Mauro
Journal: Leukemia (2023)

Asciminib, the first BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket (STAMP), is approved worldwide for the treatment of adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) treated with ≥2 prior tyrosine kinase inhibitors (TKIs). In ASCEMBL, patients with CML-CP treated with ≥2 prior TKIs were randomized (stratified by baseline major cytogenetic response [MCyR]) 2:1 to asciminib 40 mg twice daily or bosutinib 500 mg once daily. Consistent with previously published primary analysis results, after a median follow-up of 2.3 years, asciminib continued to demonstrate superior efficacy and better safety and tolerability than bosutinib. The major molecular response (MMR) rate at week 96 (key secondary endpoint) was 37.6% with asciminib vs 15.8% with bosutinib; the MMR rate difference between the arms, after adjusting for baseline MCyR, was 21.7% (95% CI, 10.53-32.95; two-sided p = 0.001). Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs.